1. Field of the Invention
The present invention relates to novel hydroquinone derivatives useful as intermdiates in the synthesis of coenzyme Q, vitamin K and the polyprenyl-trimethylquinones and to a novel process for the preparation of such derivatives.
2. Description of the Prior Art
Quinones having polyprenyl side chains, such as vitamin K and coenzyme Q, and reflecting the following structural formulae, are important medicinal chemicals: ##STR3## wherein n represents the number of isoprene units.
The compounds of the aforenoted structural formulae wherein n is 1-12 are known [cf., e.g., R. H. Thomson, Naturally Occurring Quinones, second edition, Academic Press (1971) and Helvetica Chimica Acta, 46, 2517 (1963)]. These compounds may, depending upon the number of the isoprene units, exhibit different pharmacological activities. In this respect, and insofar as the stereochemistry of the double bonds in the polyisoprene chain is concerned, an all-trans geometry is considered the more desirable.
A process has been known for a relatively long period of time for the synthesis of such quinones, which process comprises, utilizing the synthesis of coenzyme Q as an example, reacting 2,3-dimethoxy-5-methyl-hydroquinone (aromatic nucleus) with a prenyl alcohol or derivative thereof and oxidizing the resultant condensation product to the corresponding quinone [see, e.g., British Patent Specification No. 928,161; Chemical Abstracts, 74, 125168 v, (1971)].
The above process is illustrated by the following reaction sequence: ##STR4##
The above condensation may be carried out in the presence of an acid catalyst, such as formic acid, sulfuric acid, hydrochloric acid, phosphoric acid, p-toluenesulfonic acid or another protic acid, or zinc chloride, aluminum chloride, boron trifluoride etherate or another Lewis acid. However, said reaction is accompanied by such side reactions as cyclization within the polyprenyl side chain and chromanol cyclization of the condensation product, and as a result the yield of the desired compounds is at most 30%. To avoid this disadvantage, there have been proposed, for example, (i) a method which comprises reacting a 2,3-dimethoxy-5-methylhydroquinone dimethoxymethylether-6-magnesium halide as the aromatic nucleus-forming substance with a .pi.-allylic nickel complex of a polyprenyl halide, (ii) a method which comprises reacting said aromatic nucleus-forming substance with a polyprenyl halide in the presence of palladium chloride or dichlorobis(triphenyl-phosphine) nickel as catalyst [Chemical Abstracts, 84, 179876z and 179877a (1976)], (iii) a method which comprises reacting a 2,3-dimethoxy-5-methyl-6-halo-hydroquinone diacetate (aromatic nucleus-forming substance) with a .pi.-allylic nickel complex of a polyprenyl halide [British Patent Specifications Nos. 1,424,004 and 1,426,769], and (iv) a method which comprises reacting 2,3-dimethoxy-5-methylhydroquinone borate ester with a prenyl alcohol or derivative thereof [British Patent Specification No. 1,529,326 and U.S. Pat. No. 4,061,660].
While the reaction yield can indeed be improved to some extent by the immediately aforesaid methods, the stereo-selectivity, which is another important problem in obtaining all-trans isomers, is not at all improved. For example, in the event that solanesol, which is an all-trans C.sub.45 polyprenyl alcohol and obtainable by extraction, e.g., from natural tobacco leaf or potato leaf, is subjected to chain extension to C.sub.50 and then to condensation with an aromatic nucleus, a mixture of stereoisomers is obtained in which the cis/trans ratio is typically between about 3/7 to 2/8. The purification procedure for recovering the trans isomer from said mixture is, however, very complicated and, moreover, the structural components (i.e., the side chain and aromatic nucleus) constituting the separated cis isomer are completely lost. Accordingly, a serious need exists in this art to overcome all of the aforenoted disadvantages.